SCN5A Variant I1347N

Summary of observed carriers, functional annotations, and structural context for SCN5A I1347N. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/10 effective observations

Estimated BrS1 penetrance

46%

4/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

I1347N has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 4 individuals for Brugada syndrome and 0 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
NA NA NA 0.93 67 1

PROVEAN scores below -2 suggest deleterious impact. REVEL scores above 0.5–0.75 are often interpreted as likely pathogenic. PolyPhen-2 scores above 0.85 are typically pathogenic. Penetrance density summarises neighbouring residue risk (Kroncke et al. 2019).

Reported carrier data

Observed carriers by publication or cohort.
Source Year Carriers Unaffected LQT3 BrS1 Other Other Disease
Literature, cohort, and gnomAD – 0 0 0 0 –
Variant features alone – 15 11 0 4 – –

Totals may differ from individual publications due to duplicate patients removed during curation.

Nearby variants

Neighbouring residues within 15 Ångström provide structural context. Variants listed in the right-most column have been observed clinically or in gnomAD.

Previously observed variants near I1347N.
Neighbour residue Distance (Å) Observed variants
1355 13
811 12 R811H, c.2435_2436+3delTGGTAinsCGCCT, R811G,
808 13 R808H, R808C, R808P,
1352 10
1406 14 G1406R, G1406E, G1406R,
1340 11 V1340I,
1457 11
1453 10
1455 14
1339 12 p.L1339del, L1339F
1351 6 M1351R, M1351V,
1449 11 Y1449S, Y1449C,
1452 11
1461 13 T1461S, T1461S,
812 6 L812Q,
1350 6 I1350L, I1350T,
1344 6 F1344L, F1344S, F1344L, F1344L,
731 10 T731I,
806 15 V806M,
1450 13
819 12
818 11
1411 14
1451 15 V1451L, V1451D,
1353 11 V1353M,
825 12
1407 15
737 13
1458 15 S1458Y,
1348 5 F1348L, F1348L, F1348L,
1404 15
1349 6
822 14 W822X, W822C, W822C,
788 15 I788V,
1346 5 L1346P, L1346I,
1341 10
1356 14 c.4066_4068delTT,
728 14 V728I,
1412 11 L1412F,
810 12
727 13
1408 12 G1408R, G1408R,
735 11 A735V, A735T, A735E,
1456 10
732 13
734 9 M734V, c.2201dupT,
814 11 R814Q,
1460 14 F1460L, F1460L, F1460L,
816 7 F816L, F816L, F816Y, F816L,
813 9 c.2436+12G>A, c.2437-5C>A,
1454 14
1338 15 L1338V,
1354 11
817 13 K817E,
1405 11 V1405M, V1405L, V1405L,
809 10
1409 11 Y1409X, Y1409C,
815 6
1343 7
1345 8 W1345C, W1345C,
1342 9
784 14 F784L, F784L, F784L,
1416 15 c.4245+1G>C, A1416G, A1416E, c.4245+2T>A, c.4245+1G>A,
736 15 L736P,
730 13 N730K, N730K,
1347 0
1415 15
829 14
828 14 L828V,
1402 13
1413 14